PALO ALTO, CA — Medication is only effective if taken, yet how to make sure patients maintain adherence with anticoagulants and many other long-term medications for chronic diseases poses one of the greatest dilemmas for healthcare providers.

In an effort to meet the challenge, the VA is turning to pharmacists to do more than just dispense drugs. It has found that a combination of scheduled pharmacist follow-up and safety monitoring can boost patient adherence for the novel anticoagulant dabigatran above 80%, a notable increase from the 50% or less seen for statins, antihypertensives and other long-term treatments of asymptomatic conditions such as atrial fibrillation.

Researchers at the VA Palo Alto Health Care System (VAPAHCS) undertook a study to determine the effectiveness of pharmacist monitoring of medication possession ratios (MPRs) of patients on dabigatran for atrial fibrillation or flutter through anticoagulation clinics. While the results were not what they expected, the findings still provide useful information for clinicians concerned about adherence to oral anticoagulant regimens and, potentially, other medications.

“Based on our results, it might seem that pharmacist follow-up has little bearing on MPR or adherence, but this may be because of bias introduced by the need to conduct an interim safety analysis,” said Pei-Yu Lee, PharmD, clinical pharmacist at the Palo Alto VAMC and lead researcher. The study showed that patients in both usual care and receiving pharmacist follow-up had adherence rates above 80%. Following the presentation of interim results, however, the researchers were instructed to conduct safety monitoring on the usual-care patients, which resulted in interventions in six cases.

The role of pharmacists is increasing to include a larger role in patient care. In this photo, Hiral Patel, PharmD, a resident at Veterans Affairs North Texas Health Care System in Dallas, consults with a patient. Patel plans to focus her pharmacy practice on chronic disease state management of patients with diabetes, hypertension, hyperlipidemia, and cardiovascular disease.

“We looked at the adherence data every day and saw we needed to do something for those who were not achieving adherence rates of 80% as measured by medication possession ratios. We contacted the doctors and asked why patients weren’t refilling their prescriptions. Ethically we couldn’t look at the data and not do anything about it for the usual-care patients because of the risk of stroke,” Lee told U.S. Medicine. Providers were contacted again if patients continued to have MPRs below 80% in subsequent months. Communication continued until patients reached the 80% rate, discontinued the drug or the study ended.

As a result, the adherence rate for patients receiving usual care is almost certainly overstated. “We don’t know what the true MPR for usual care is, but it seems there is a need for some kind of intervention to keep adherence above 80%,” she noted.

Unlike warfarin, dabigatran requires limited ongoing monitoring in usual care. The criteria for use stipulates that patients have baseline laboratory values performed within three months of starting therapy and, since Oct. 26, 2011, the VA Pharmacy Benefits Management Services (PBM) has required follow-up over the first three months of treatment. VAPAHCS decided the pharmacists in the existing anticoagulation clinic (ACC) would monitor dabigatran patients during their initial three months to determine mean rate of adherence to therapy based on MPRs and the frequency of bleeding episodes, strokes and venous thromboembolism.

During the study period, patients received an initial consultation to discuss the importance of the twice-daily dosing regimen, potential side effects, refill procedures and proper storage of the medication. Dabigatran must be kept in its original packaging, either a blister pack or special pill bottle, because of its sensitivity to moisture, Lee noted. Pharmacists followed up with patients in person or by phone at two weeks, one month and three months.

The 20 patients in the monitored group were compared with 48 patients in the usual-care group, who received dabigatran prescriptions prior to the drug’s addition to the VA formulary and establishment of monitoring guidelines. Pharmacists monitored patients daily using the Computerized Patient Record System and a specially designed dabigatran adherence dashboard.

All study participants monitored by pharmacists refilled their medication at least once, whereas three of the 48 patients in the usual-care group did not. Only 10% of ACC-monitored patients were nonadherent at the three-month mark, compared with 25% of those receiving usual care, although the researchers noted that the difference was not statistically significant. Overall, the mean MPR for the pharmacist-monitored group was 93.1%, compared with 88.4% for those in usual care.

No patients in either group experienced thromboembolic events or strokes. In the usual-care group, two patients had minor bleeding, as did one patient among those monitored by pharmacists. One patient had major bleeding in the usual-care group. He stayed on dabigatran after treatment. None in the monitored group had a significant bleeding episode.

In the published study, which appeared in the American Journal of Health-System Pharmacy, the authors noted that using MPR as a proxy for adherence may bias results toward adherence as its dependence on two fill dates excludes patients who never refill their medication. It also cannot ascertain whether patients took the medications after picking up their prescriptions. 1

In addition, 85% of patients in the pharmacist-monitored group had been transitioned from warfarin and were, therefore, more accustomed to monitoring and aware of the importance of adherence. In the usual-care group, 50% had previously been prescribed warfarin.

Other researchers at the Palo Alto facility are conducting studies that look at the impact of pharmacist follow-up with patients on dabigatran over a longer period and with larger numbers of participants.